The present invention relates to wireless communication capability of an external stimulator for neuromodulation, more specifically an external stimulator for neuromodulation therapy for urological, neurological, and neuropsychiatric disorders, having two-way wireless communication through a server.
Biological and human clinical research has shown utility of electrical nerve stimulation therapy for urinary incontinence and a broad group of neurological disorders. This invention is directed to remotely controlling the stimulation therapy for these disorders, utilizing an implanted lead-receiver, and an external stimulator with predetermined (pre-packaged) stimulation programs. Some of the predetermined programs may be manually operated, but some programs are locked-out to the patient. These patient locked-out programs can be accessed by the physician either in person via a password or remotely. The remote activation of these programs is via the wireless Internet server, communicating with an external controller using a wireless interface. A physician situated remotely is also able to activate predetermined programs, as well as, interrogate the external stimulation devices of his/her patients. In addition, a physician is able to change which programs are accessible to the patient.
In considering first, the background of urinary urge incontinence. FIG. 1 shows a sagittal section of the human female pelvis showing the bladder 10 and urethra 13, in relation to other anatomic structures. Urinary continence requires a relaxed bladder during the collecting phase and permanent closure of the urethra 13, whereas at micturition (urination), an intravesical pressure above the opening pressure of the simultaneously relaxing urethra has to be generated. These functions of the bladder 10 and urethra 13 are centrally coordinated and non-separable. At bladder filling, the sensation of urge is mediated by slowly adapting mechanoreceptors in the bladder wall and the same receptors provide the triggering signal for micturition and the main driving force for a sustained micturition contraction. The mechanoreceptors are, technically speaking, tension receptors. It has been found that they respond equally well to tension increases induced passively by bladder filling and those induced actively by a detrusor contraction. These receptors have high dynamic sensitivity and are easily activated by external pressure transients, as may occur during coughing or tapping of the abdominal wall. Their faithful response to active changes in bladder pressure is well illustrated.
When sufficiently activated, the mechanorecptors trigger a coordinated micturition reflex via a center in the upper pons 88, as depicted schematically in FIG. 2. The reflex detrusor 92 (muscle in the wall of the urinary bladder) contraction generates an increased bladder pressure and an even stronger activation of the mechanoreceptors. Their activity in turn reinforces the pelvic motor output to the bladder 10, which leads to a further increase in pressure and more receptor activation and so on. In this way, the detrusor 92 contraction is to a large extent self generating once initiated. Such a control mechanism usually is referred to as a positive feedback, and it may explain the typical all-or-nothing behavior of the parasympathetic motor output to the bladder 10. Once urine enters the urethra, the contraction is further enhanced by reflex excitation from urethral receptors. Quantitatively, the bladder receptors are most important.
A great advantage of the positive feedback system is that it ascertains a complete emptying of the bladder 10 during micturition. As long as there is any fluid left in the lumen, the intravesical pressure will be maintained above the threshold for the mechanoreceptors and thus provide a continuous driving force for the detrusor 92. A drawback with this system is that it can easily become unstable. Any stimulus that elicits a small burst of impulses in mechanoreceptor afferents may trigger a fullblown micturition reflex. To prevent this from happening during the filling phase, the neuronal system controlling the bladder is equipped with several safety devices both at the spinal and supraspinal levels.
The best-known spinal mechanism is the reflex control of the striated urethral sphincter 90, which increases its activity in response to bladder mechanoreceptor activation during filling. An analogous mechanism is Edvardsen""s reflex, which involves machanoreceptor activation of inhibitory sympathetic neurons to the bladder. The sympathetic efferents have a dual inhibitory effect, acting both at the postganglionic neurons in the vesical ganglia and directly on the detrusor muscle of the bladder 92. The sphincter and sympathetic reflexes are automatically turned off at the spinal cord level during a normal micturition. At the supraspinal level, there are inhibitory connections from the cerebral cortex and hypothalamus to the pontine micturition center. The pathways are involved in the voluntry control of continance. Other inhibitory systems seem to orignate from the pontine and medullary parts of the brainstem with at least partly descending connections.
Bladder over-activity and urinary urge incontinance may result from an imbalance between the excitatory positive feedback system of the bladder 10 and inhibitory control systems causing a hyperexcitable voiding reflex. Such an imbalance may occur after macroscopic lesions at many sites in the nervous system or after minor functional disturbances of the excitatory or inhibitory circuits. Urge incontinence due to detrusor instability seldom disappears spontaneoulsly. The symptomatic pattern also usually is consistent over long periods.
Based on clinical experience, subtypes of urge incontinance include, Phasic detrusor instability and uninhibited overactive bladder. Phasic detrusor instability is characterized by normal or increased bladder sensation, phasic bladder contractions occurring spontaneously during bladder filling or on provocation, such as by rapid filling, coughing, or jumping. This condition results from a minor imbalance between the bladder""s positive-feedback system and the spinal inhibitory mechanisms. Uninhibited overactive bladder is characterized by loss of voluntary control of micturition and impairment of bladder sensation. The first sensation of filling is experienced at a normal or lowered volume and is almost immediately followed by involuntary micturition. The patient does not experience a desire to void until she/he is already voiding with a sustained detrusor contraction and a concomitant relaxation of the urethra, i.e., a well-coordinated micturitiori reflex. At this stage, she/he is unable to interrupt micturition voluntarily. The sensory disturbance of these subjects is not in the periphery, at the level of bladder mechanoreceptors, as the micturition reflex occurs at normal or even small bladder volumes. More likely, the suprapontine sensory projection to the cortex is affected. Such a site is consistent with the coordinated micturition and the lack of voluntary control. The uninhibited overactive bladder is present in neurogenic dysfunction.
Patients with stress and urge incontinence are difficult to treat adequately. Drug treatment often is insufficient and, even when effective, does not lead to restoration of a normal micturition pattern. Since bladder over-activity results from defective central inhibition, it seems logical to improve the situation by reinforcing some other inhibitory system. Successful therapy of the urge component does not influence the stress incontinence. While an operation for stress incontinence sometimes results in deterioration of urgency. Electrostimulation is a logical alternative in mixed stress and urge incontinence, since the method improves urethral closure as well as bladder control
Neuromodulation is a technique that uses electrical stimulation of the sacral nerves 85, (a general diagram of spinal cord and sacral nerves 85 is shown in FIG. 3). The aim of this treatment modality is to achieve detrusor 92 inhibition by chronic electrical stimulation of afferent somatic sacral nerve fibers 85 via implanted electrodes connected to a subcutaneously placed pulse generation means.
The rationale of this treatment modality is based on the existence of spinal inhibitory systems that are capable of interrupting a detrusor 92 contraction. Inhibition can be achieved by electrical stimulation of afferent anorectal branches of the pelvic nerve, afferent sensory fibers in the pudendal nerve and muscle afferents from the limbs. Most of these branches and fibers reach the spinal cord via the dorsal roots of the sacral nerves 85. Of the sacral nerve roots the S3 root is the most practical for use in chronic electrical stimulation. In neuromodulation, the entire innervation system should be intact. As shown schematically in FIG. 4, the procedure consists of placing electrodes 61,62 in one of the sacral foramen as close to the pelvic plexus and pudendal nerve as possible and connecting the lead 59 with a means for electrical stimulation 49. An anchoring sleeve 15 may be used for securing the lead.
The hypothesis behind neuromodulation of the sacral roots (sensory and motor) is to correct, by the use of regulating electrical impulses, the dys-synergic activities of the cholinergic, adrenergic, and motor reflex pathways that initiate vesical storage and micturition. Although some theories have been developed that explain the effects of neuromodulation, most of the results are based on empiric findings in human studies. Some animal experiments and electrophysiologic studies in humans show there is a spinal inhibitory action through the afferent branches of the pelvic and pudendal nerves. It is not clear whether neuromodulation primarily influences the micturiction center located near the thalamus 25. Some maintain that there is a direct correction of the dys-synergis of the pelvic floor (pudendal nerve) by influencing the abnormal contractility of the pelvic floor.
A neurophysiological explanation for the effectiveness of this treatment modality in detrusor instability is based on animal experiments and electrophysiological studies in humans. Electrical stimulation for the treatment of urinary incontinence has evolved over the past 40 years. The mechanism of action of electrical stimulation was investigated initially in animal models. Over 100 years ago, Griffiths demonstrated relaxation of a contracted detrusor during stimulation of the proximal pudendal nerve in the cat model and further work clarified the role of pudendal afferents in relation of the detrusor 92. Spinal inhibitory systems capable of interrupting a detrusor 92 contraction can be activated by electrical stimulation of afferent anorectal branhes of the pelvic nerve, afferent sensory fibers in the pudendal nerve and muscle afferents from the limbs. The effectiveness of neuromodulation in humans has been objectively demonstrated by urodynamic improvement, expecially in light of the fact that such effects have not been noted in drug trials.
Neuromodulation also acts on neural reflexes but does so internally by stimulation of the sacral nerves 85. Sacral nerve 85 stimulation is based on research dedicated to the understanding of the voiding reflex as well as the role and influence of the sacral nerves 85 on voiding behavior. This research led to the development of a technique to modulate dysfunctional voiding behavior through sacral nerve stimulation. It is thought that sacral nerve stimulation induces reflex mediated inhibitory effects on the detrusor 92 through afferent and/or efferent stimulation of the sacral nerves 85. Even though the precise mechanism of action of electrical stimulation in humans is not fully understood, it has been shown that sensory input traveling through the pudendal nerve can inhibit detrusor activity in humans. Most experts believe that non-implanted electrical stimulation works by stimulating the pudendal nerve afferents, with the efferent outflow causing contraction of the striated pelvic musculature. There is also inhibition of inappropriate detrusor activity.
In summary, the rationale for neuromodulation in the treatment of such patients is the observation that stimulation of the sacral nerves via electrical stimulation can inhibit inappropriate neural reflex behavior.
Moving now to the background of neurological disorders. Adjunct therapy for neurological disorders such as partial complex epilepsy, generalized epilepsy, depression, Alzheimer""s disease, and several other disorders related to neuromodulation of the vagus nerve. Biological research has shown beneficial medical effects of vagus nerve stimulation (VNS) for patients with the above disorders.
Vagus nerve stimulation, and the profound effects of electrical stimulation of the vagus nerve on central nervous system (CNS) activity, extends back to the 1930""s. Medical studies in clinical neurobiology have advanced our understanding of anatomic and physiologic basis of the beneficial neurologic effects of chronic vagus nerve stimulation.
Some of the somatic interventions for the treatment of depression and the like, include electroconvulsive therapy (ECT), transcranical magnetic stimulation, vagus nerve stimulation, and deep brain stimulation. The vagus nerve 54 is the 10th cranial nerve, and is a direct extension of the brain. FIG. 5, shows a diagram of the brain and spinal cord, with its relationship to the vagus nerve 54 and the nucleus tractus solitarius 14. FIG. 6 shows a diagram of base of the brain, showing the relationship of the vagus nerve with the other eleven cranial nerves.
Vagus nerve stimulation is a means of directly affecting central function and is less invasive than deep brain stimulation (DBS). As shown in FIG. 7, cranial nerves have both afferent pathway 19 (inward conducting nerve fibers which convey impulses toward the brain) and efferent pathway 21 (outward conducting nerve fibers which convey impulses to an effector). The vagus nerve 54 is composed of 80% afferent sensory fibers carrying information to the brain from the head, neck, thorax, and abdomen. The sensory afferent cell bodies of the vagus reside in the nodose ganglion and relays information to the nucleus tractus solitarius (NTS).
As shown schematically in FIG. 8, the nucleus of the solitary tract 14 relays this incoming sensory information to the rest of the brain through three main pathways; 1) an autonomic feedback loop, 2) direct projection to the reticular formation in the medulla, and 3) ascending projections to the forebrain largely through the parabrachial nucleus 20 (PBN) and the locus ceruleius 22 (LC). The PBN sits adjacent to the LC (FIG. 5). The PBN/LC sends direct connections to every level of the forebrain, including the hypothalamus 26, and several thalamic regions that control the insula and orbitofrontal 28 and prefrontal cortices. Perhaps important for mood regulation, the PBN/LC has direct connections to the amygdala 27 and the bed nucleus of the stria terminalisxe2x80x94structures that are implicated in emotion recognition and mood regulation.
In sum, incoming sensory (afferent) connections of the vagus nerve 54 provide direct projections to many of the brain regions implicated in neurologic and neuropsychiatric disorders. These connections reveal how vagus nerve 54 stimulation is a portal to the brainstem and connected regions. These circuits likely account for the beneficial neurologic and neuropsychiatric effects of the vag us nerve stimulation.
Increased activity of the vagus nerve 54 is also associated with the release of more serotonin in the brain. Much of the pharmacologic therapy for treatment of migraines is aimed at increasing the levels of serotonin in the brain. Therefore, non-pharmacologic therapy of electrically stimulating the vagus nerve 54 would have benefits for adjunct treatment of migraines also.
The vagus nerve 54 provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Other cranial nerves can be used for the same purpose, but the vagus nerve 54 is preferred because of its easy accessibility. In the human body there are two vagus nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagus nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagus nerve does not cause any significant deleterious side effects.
Most nerves in the human body are composed of thousands of fibers, of different sizes designated by groups A, B and C, which carry signals to and from the brain. The vagus nerve 54, for example, may have approximately 100,000 fibers of the three different types, each carrying signals. Each axon or fiber (shown in FIG. 9A) of that nerve conducts only in one direction, in normal circumstances. The A and B fibers are myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat, as shown in FIG. 9B), whereas the C fibers are unmyelinated.
A commonly used nomenclature for peripheral nerve fibers, using Roman and Greek letters, is given in the table below:
The diameters of group A and group B fibers include the thickness of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter. Group B fibers are not present in the nerves of the limbs; they occur in white rami and some cranial nerves.
Compared to unmyelinated fibers, myelinated fibers are typically larger, conduct faster, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (xcexcs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 xcexcs) and a higher amplitude for activation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.
The vagus nerve is composed of somatic and visceral afferents and efferents. Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible, however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagus nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull. The central projections terminate largely in the nucleus of the solitary tract 14 which sends fibers to various regions of the brain (e.g., the hypothalamus 26, thalamus 25, and amygdala 27).
In summary the basic premise of vagus nerve 54 stimulation for relief of neurological disorders is that vagus visceral afferents have a diffuse central nervous system (CNS) projection, and activation of these pathways has a widespread effect on neuronal excitability.
One form of prior art neuromodulation therapy is generally directed to an implantable pulse generator system. In such a system, the communication is generally performed via a modified personnel computer and a programming wand.
Prior art wireless communication for medical stimulation devices includes, U.S. Pat. No. 5,759,199 (Snell et al) which is directed to ambulatory monitoring and programming of an implantable medical device. The system disclosed enables wireless communication between the programmer/analyzer and the implantable medical device.
U.S. Pat. No. 5,978,713 (Prutchi) is primarily directed to telemetry of information from an implant that is generated from atrial and ventricular endocardial leads to an external programmer.
U.S. Pat. No. 5,997,476 (Brown) is directed to communicating information to an individual and for remotely monitoring the individual. The system of the ""476 patent includes a server and a remote interface for entering in the server a set of queries to be answered by the individual. The disclosed system includes a remotely programmable apparatus connected to the server via a communication network.
U.S. Pat. No. 5,458,122 (Hethuin) is directed to the wireless transmission of surface EKG signals to a remote location via transmission equipment components held onto the body of the patient.
One form of prior art for neuromodulation therapy, generally includes implantable pulse generators. U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like and are directed to stimulating the vagus nerve by using xe2x80x9cpacemaker-likexe2x80x9d technology, such as an implantable pulse generator. The pacemaker technology concept consists of a stimulating lead connected to a pulse generator (containing the circuitry and DC power source) implanted subcutaneous or submuscularly, somewhere in the pectoral or axillary region, with an external personal computer (PC) based programmer. Once the pulse generator is programmed for the patient, the fully functional circuitry and power source are fully implanted within the patient""s body. In such a system, when the battery is depleted, a surgical procedure is required to disconnect and replace the entire pulse generator (circuitry and power source). These patents neither anticipate practical problems of an inductively coupled system for adjunct therapy of epilepsy, nor suggest solutions to the same for an inductively coupled system for adjunct therapy of partial complex or generalized epilepsy.
U.S. Pat. No. 5,215,086 (Terry, Jr. et al) is directed to the use of implantable pulse generator technology for treating and controlling migraine, by stimulating the vagus nerve of a patient by an implantable lead and xe2x80x9cpacemaker likexe2x80x9d device to alleviate the migraine attack.
U.S. Pat. No. 4,771,779 (Tanagho et al) is directed to a system for controlling bladder evacuation, which consists of multiple implanted stimulation systems having electrodes positioned on nerves controlling external sphincter and bladder functions, and electronic control system which transmit to the stimulation systems. In this patent, by having multiple stimulation systems and means of controlling them, the interaction between stimulating the bladder and external sphincter can be controlled.
The present invention is directed to a system and method for remotely controlling the neuromodulation therapy of urological, neurological, neuropsychiatric disorders. The system comprises an implantable lead-receiver, and an external stimulator with the primary coil on the same packaging. The implanted lead-receiver and the external stimulator are inductively coupled. The external stimulator has two way wireless communication capabilities. This wireless capability is used primarily to exchange the programmed parameters in the stimulator to remotely control the stimulation therapy.
An implanted lead-receiver contains electrodes in contact with the nerve to be stimulated, passive circuitry, and a secondary coil for coupling with an external (primary) coil. The external stimulator comprises a unit, which is about the size of a small cardiac pacemaker on which a coil and pulse generator circuitry with a replaceable power source (battery) module are mounted. The pulse generator battery is the disposable component of the system. An indicator on the external stimulator indicates the battery status, so that the battery can be routinely replaced. Proximity sensing circuitry aids in the optimal placement of the external stimulator coil, in close proximity to the secondary (implanted) coil. The combination of a magnet in the implanted lead-receiver and sensors mounted in the external generator, provide means for proximity sensing and feedback control of pulse stimulus outputs. The feedback circuitry adjusts the output of pulses to ensure proper delivery of electrical stimulation therapy as the primary (external) and secondary (implanted) coils change orientation relative to each other. The external stimulator contains a limited number of predetermined (pre-packaged) programs consisting of unique combinations of parameters such as pulse amplitude, pulse width, frequency of stimulation, on-time, and off-time.
In one aspect of the invention, the external stimulator communicates wirelessly with a remote server, using a communication protocol such as wireless application protocol (WAP). A physician who may be situated remotely, is able to access information regarding the pulse generation programs that the stimulator is currently using to deliver pulse signals to the patient. The physician can change the therapy to another predetermined program by communicating with the server. The server in turn communicates with the neurostimulator (external pulse generator). The physician can also make relatively xe2x80x9csmallxe2x80x9d variations to existing programs for improvements in therapy being delivered. The communication between physician""s handheld device and server, and communication between the server and external neurostimulator utilizes the wireless application protocol (WAP).
In another aspect of the invention, a physician at a remote location, using a wireless handheld device, is able to check the stimulation program execution status of his/her patient population by obtaining a summary report, using secure communication.
In yet another aspect of the invention, the physician is able to set up long-term schedules of stimulation therapy for their patient population, through wireless communication with the server. The server in turn communicates these programs to the neuro-stimulator. For instance, a physician may program an Alzheimer""s patient to a stimulation program for two weeks, and program an epilepsy patient to long-term xe2x80x9conxe2x80x9d, xe2x80x9coffxe2x80x9d stimulation therapy. Each schedule is securely maintained on the server, and is editable by the physician, and can get uploaded to the patient""s stimulator device at a scheduled time. Each device issued to a patient has a unique identification key in order to guarantee secure communication between the wireless server and device.